Indevus Receives Approvable Letter from FDA for NEBIDO(R)
The FDA has expressed a concern about a relatively small number ofpatients in European post-marketing use who have experienced respiratorysymptoms immediately following the intramuscular injection of NEBIDO 1000 mg,4 cc injection volume, (versus the 750 mg, 3 cc injection volume used in theUnited States). The Company believes and the FDA concurs that the reaction islikely the result of a small amount of the oily solution immediately enteringthe vascular system from the injection site, a known, rare complication ofoil-based depot injections.
The phenomenon is characterized by short-term reactions involving an urgeto cough, coughing episodes or a shortness of breath. In rare cases thereaction has been classified as serious or the patient experiences othersymptoms such as dizziness, flushing or fainting. In the Company's U.S.clinical trials of NEBIDO 750 mg (3 cc injection volume), the proposed dose inthe U.S., there was a single, mild, non-serious case of oil-based coughobserved. In addition, the FDA believes that four cases in the Europeanpost-marketing experience may have an allergic, anaphylactoid component,although the Company believes these cases were improperly classified andrepresent the same oil-based phenomenon.
The FDA has requested the Company address these clinical deficiencies byproviding detailed safety information from clinical studies to determine theprecise incidence of serious post-injection oil-based reactions and allergicreactions. Specifically, the FDA has requested follow-up data from theon-going U.S. and European studies in which patients are being treated withNEBIDO on an extended basis. A majority of these trials are scheduled to becompleted within twelve months. The FDA stated that depending on the findings,the number of subjects and the number of injections of testosteroneundecanoate from the studies listed above, the safety database may need toinclude data from additional clinical studies. They have requested that theCompany propose the size of the safety database (i.e., total number ofsubjects exposed to testosterone undecanoate intramuscular injection and totalnumber of injections) and the rationale for the size of the proposed safetydatabase.
FDA has also requested the Company provide a plan to minimize the risksassociated with the clinical use of testosterone undecanoate intramuscularinjection, namely, to reduce the incidence and/or severity of the seriousoil-based reactions and has requested certain in vitro and skin-testing datato exclude an allergic component to the drug or some of its excipients.
Glenn L. Cooper, M.D., chairman and chief executive officer of Indevusstated, "We believe that NEBIDO is a safe and effective drug for its intendeduse and continue to be disappointed that the FDA was not willing to approvethe drug at this time with adequate labeling of the oil-based reactions andhow to minimize them with proper injection technique. However, we areencouraged that this approvable letter provides a road map for the product'seventual approval. We will work with the FDA and our partner, Bayer ScheringPharma AG, to respond to the approvable letter and devise a plan to addressthe deficiencies. While the FDA has not specifically requested additionalclinical studies, we believe that an additional study will likely be requiredto
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